DNA Polymerase: Structural Homology, Conformational Dynamics, and the Effects of Carcinogenic DNA Adducts
Figure 1
Structure of Klentaq1 (a) Structure of Klentaq1 in the absence of DNA (PDB #1KTQ) [7]. The overall structure of polymerases resembles that of a human right hand forming palm (yellow), fingers (green), and thumb (blue) domains. The palm domain houses the active site residues responsible for the to polymerase activity, and the to exonuclease domain (red) allows excision of misincorporated bases. The H1H2 Loop is disordered and missing from the structure (ends connected with orange line). (b) Klentaq1 open binary complex (PDB #4KTQ) [8]. The DNA is situated in the cleft formed between the fingers, thumb, and palm domains. The Y671 residue (pink) is stacked on top of the template (dark blue). K540 (brown) makes nonspecific interactions with the minor groove to aid in holding the polymerase bound to the DNA. Helices I (cyan) and H (orange) make small movements relative to their positions in the open complex, and the H1H2 loop (light green) now becomes ordered and visible in the structure. The remainder of the colors are as follows primer (red), H1 and H2 helix (light green), O helix (yellow), and N helix (green). (c) Klentaq1 closed ternary complex (PDB #3KTQ) [8]. A correctly base pairing ddCTP (light blue) is located within the active site inducing a large conformational change of the O (yellow) and N (green) helices (compare with positions in (b)). Y671 is now flipped out of its stacking arrangement with the template and the templating base forms Watson-Crick base pairs with the ddCTP. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081) [6].
